The field of the invention is treatment of radionuclide contamination with calcium diethylenetriaminepentaacetate (Ca-DTPA) and zinc diethylenetriaminepentaacetate (Zn-DTPA).
Ca-DTPA and Zn-DTPA pentetate have been shown to be effective in treating internal contamination with radionuclides such as plutonium, americium, or curium. DTPA increases the rates of elimination of these substances from the body through the exchange of calcium or zinc ions with the transuranium element. The transuranium-DTPA complex is stable and is excreted in urine.
Formulations of Ca-DTPA and Zn-DTPA suitable for intravenous administration, or inhalation via nebulizer, were approved by the FDA in August 2004 for the elimination of known or suspected internal contamination with the transuranic metals (Z>92) plutonium, americium, and curium.
Other formulations (for example oral, inhalation or transdermal) would be more easily administered than the injectable formulations; however, because of its hydrophilicity, DTPA is poorly absorbed when administered by these routes. Oral administration of Ca-DTPA and Zn-DTPA for radionuclide chelation has been described (Kostial et al, Int. J. Radiat. Biol (1987) 52:501-504; Volfet al, Int J Radiat Biol (1999) 75:929-41); and Durbin et al., Radiat Prot Dosimetry (2003) 105:503-8.); however, formulations that increase the oral bioavailability of Ca-DTPA or Zn-DTPA have not been reported.
The National Instituted of Allergy and Infectious Diseases (NIAID) issued a solicitation (RFP-NIH-NIAID-DAIT-05-46 “Development of Improved DTPA for Radionuclide Chelation”, Apr. 26, 2005) stating its interest in facilitating the discovery and demonstration of proof-of-concept of prodrugs, alternative formulations, or alternative delivery methods of DTPA that provide for plasma levels sufficient to decorporate systemic transuranic compounds for use by the general public in the case of a radiation emergency.